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Thesis
Genetic basis of gender bias in neuroinflammatory diseases such as multiple sclerosis
Master of Science (M.S.), Drexel University
May 2024
DOI:
https://doi.org/10.17918/00010447
Abstract
Diseases such as Multiple Sclerosis (MS), a chronic neuroinflammatory demyelinating disorder, affect more women than men. This gender bias is linked to genes on the X-chromosome, which has two copies in females compared to a single copy in males. The neuroimmune pathogenesis of MS is complex and governed by the infiltration of immune cells into the central nervous system (CNS). There has been extensive research, seeking to understand X-chromosome linkage with MS; however, not related to leukocyte trafficking. Blocking immune cell entry into the CNS has been proven as a viable target for the treatment of MS and addressed the role of gender. Gender bias has been associated at both the gene and the chromosome level. Typically, gender bias is prevented or minimized by X-chromosome inactivation (XCI). Nevertheless, some genes like CXORF21 and DDX3X can escape XCI and contribute to systemic lupus erythematosus (SLE) and DDX3X Syndrome, respectively. In the case of MS, immune cells such as T cells and Dendritic cells (DCs) move to the CNS. Due to persistent tissue stress, these cells may induce local inflammation and autoimmunity, leading to neurodegeneration, onset, and progression of MS. Chemokines are signaling proteins that regulate leukocyte trafficking to the site of injury, contributing to cell recruitment, CNS inflammation, and disease severity. Interestingly, some chemokine receptors (CXCR3) are X-linked and may escape XCI. Therefore, this literature review provides a comprehensive assessment of the genetic basis behind gender bias seen in MS and other inflammatory diseases. The impact of the X-chromosome on autoimmunity, including XCI and the expression of X-linked genes is also evaluated.
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Details
- Title
- Genetic basis of gender bias in neuroinflammatory diseases such as multiple sclerosis
- Creators
- Sopiko Darchiashvili
- Contributors
- Paul McGonigle (Advisor)
- Awarding Institution
- Drexel University
- Degree Awarded
- Master of Science (M.S.)
- Publisher
- Drexel University; Philadelphia, Pennsylvania
- Number of pages
- v, 86 pages
- Resource Type
- Thesis
- Language
- English
- Academic Unit
- College of Medicine; Pharmacology and Physiology; Drexel University
- Other Identifier
- 991021874814304721